We examine molecular mechanisms and metabolic patterns in biogenic amine systems in brain and their behavioral correlates with theoretical application to clinical psychiatric syndromes in relation to drugs of abuse, psychotherapeutic drugs, and drug combinations, routinely developing and analyzing a compendium of data demonstrating differential patterns of response in the rat to specific manipulations among a dozen or so dependent variables. Specific areas of investigation are: 1) molecular mechanisms underlying lithium-ethanol interactions in the serotonergic system (relevant to modification by lithium of "high" and withdrawal phenomena in human alcoholics, an effect we predicted earlier from our neurochemical lithium/serotonin model); 2) serotonergic influence on appetitional behavior, initially satiety threshold, subsequently other neurochemical and behavioral correlates suggestive of model addictive behaviors; 3) proteolytic mechanisms that could regulate tryptophan and tryosine hydroxylases, thus influencing biogenic amine synthesis; 4) elaboration of the function of reduced pterins in tryptophan and tyrosine hydroxylation in terms of regulatory function, biogenesis, steady-state plasticity, pharmacological intervention, in vitro mechanism/pathway studies, and potential involvement in pathological states; 5) elucidation of factors determining the activity state of tryptophan hydroxylase, the dynamics of substrate availability, and adaptive regulatory changes in intraneuronal enzyme, and 6) refinement of behavioral screening measures of hallucinogens (tactile startle and holeboard paradigms) and examination of serotonergic function by means of the now validated Geyer fading measure, a cytofluorimetric gauge of serotonin concentration in the presence of catecholamines.